Novel Functions of Lipid-binding Protein 5 in Caenorhabditis elegans Fat Metabolism

Xu, Min; Joo, Hyoe Jin; Paik, Young Ki

doi:10.1074/jbc.m111.227165

Cited by 23 publications

(29 citation statements)

References 37 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…This was further supported by the severe fat accumulation observed in worms with the lbp-5 ( tm1618 ) mutant (7), suggesting insufficient transport of fatty acids to the mitochondria for β-oxidation.…”

Section: Introductionmentioning

confidence: 76%

Mutation of the lbp-5 gene alters metabolic output in Caenorhabditis elegans

Xu¹,

Choi²,

Paik³

2014

BMB Reports

Self Cite

View full text Add to dashboard Cite

Intracellular lipid-binding proteins (LBPs) impact fatty acid homeostasis in various ways, including fatty acid transport into mitochondria. However, the physiological consequences caused by mutations in genes encoding LBPs remain largely uncharacterized. Here, we explore the metabolic consequences of lbp-5 gene deficiency in terms of energy homeostasis in Caenorhabditis elegans. In addition to increased fat storage, which has previously been reported, deletion of lbp-5 attenuated mitochondrial membrane potential and increased reactive oxygen species levels. Biochemical measurement coupled to proteomic analysis of the lbp-5(tm1618) mutant revealed highly increased rates of glycolysis in this mutant. These differential expression profile data support a novel metabolic adaptation of C. elegans, in which glycolysis is activated to compensate for the energy shortage due to the insufficient mitochondrial β-oxidation of fatty acids in lbp-5 mutant worms. This report marks the first demonstration of a unique metabolic adaptation that is a consequence of LBP-5 deficiency in C. elegans. [BMB Reports 2014; 47(1): 15-20]

show abstract

Section: Introductionmentioning

confidence: 76%

Mutation of the lbp-5 gene alters metabolic output in Caenorhabditis elegans

Xu¹,

Choi²,

Paik³

2014

BMB Reports

Self Cite

View full text Add to dashboard Cite

show abstract

“…The intestine also is a major site of neutral lipid storage (29, 67). Transcripts related to lipid metabolism included apolipoprotein B paralogs ( apob-1, Fig 2B) (regulators of lipoprotein particle biogenesis and secretion); hormone sensitive lipase (a regulator of diglyceride and cholesteryl ester hydrolysis); several Niemann-Pick disease type C1/C2 protein paralogs (intracellular cholesterol transporters); 7-dihydrocholesterol reductase (cholesterol and steroid biosynthesis); ceramide glucosyltransferase (sphingolipid metabolism); and fatty acid binding protein (fatty acid transport), whose homologs are upregulated in the intestines of numerous animals (68–72) (Table S1A and Table S2A). Regulators of both complex and simple carbohydrate metabolism were also intestine enriched, such as the glucosidases lysosomal alpha-glucosidase ( gaa, Fig 2B) and beta-mannosidase ; sorbitol dehydrogenase (fructose biosynthesis); and glycogenin-2, which synthesizes glycogen, a complex polysaccharide found in cytoplasmic granules of phagocytes that may be an additional energy reserve (67, 73, 74) (Table S2A).…”

Section: Resultsmentioning

confidence: 99%

Cell-type diversity and regionalized gene expression in the planarian intestine revealed by laser-capture microdissection transcriptome profiling

Forsthoefel

Cejda

Khan

et al. 2019

Preprint

View full text Add to dashboard Cite

Organ regeneration requires precise coordination of new cell differentiation and remodeling of uninjured tissue to faithfully re-establish organ morphology and function. An atlas of gene expression and cell types in the uninjured state is therefore an essential pre-requisite for understanding how damage is repaired. Here, we use laser-capture microdissection (LCM) and RNA-Seq to define the transcriptome of the intestine of Schmidtea mediterranea, a planarian flatworm with exceptional regenerative capacity. Bioinformatic analysis of 1,844 intestine-enriched transcripts suggests extensive conservation of digestive physiology with other animals, including humans. Comparison of the intestinal transcriptome to purified absorptive intestinal cell (phagocyte) and published single-cell expression profiles confirms the identities of known intestinal cell types, and also identifies hundreds of additional transcripts with previously undetected intestinal enrichment. Furthermore, by assessing the expression patterns of 143 transcripts in situ, we discover unappreciated mediolateral regionalization of gene expression and cell-type diversity, especially among goblet cells. Demonstrating the utility of the intestinal transcriptome, we identify 22 intestine-enriched transcription factors, and find that several have distinct functional roles in the regeneration and maintenance of goblet cells. Furthermore, depletion of goblet cells inhibits planarian feeding and reduces viability. Altogether, our results show that LCM is a viable approach for assessing tissue-specific gene expression in planarians, and provide a new resource for further investigation of digestive tract regeneration, the physiological roles of intestinal cell types, and axial polarity.

show abstract

“…The C. elegans genome contains nine LBP genes and the exact functions of these individual LBPs remains unclear (Plenefisch et al, 2000). Of the C. elegans LBPs, LBP-5 appears to be the most extensively studied, whereby RNAi-mediated knockdown of lbp-5 results in fat accumulation in the intestine (Xu et al, 2011). The putative role of the C. elegans LBPs in fat accumulation is notable because a characteristic feature of the daf-2 mutants and long-lived dauers is increased fat content (Ogg et al, 1997).…”

Section: Discussionmentioning

confidence: 99%

Global Cysteine-Reactivity Profiling during Impaired Insulin/IGF-1 Signaling in C. elegans Identifies Uncharacterized Mediators of Longevity

Martell

Seo

Bak

et al. 2016

Cell Chemical Biology

View full text Add to dashboard Cite

Summary In the nematode, Caenorhabditis elegans, inactivating mutations in the insulin/IGF-1 receptor, DAF-2, result in a 2-fold increase in lifespan mediated by DAF-16, a FOXO-family transcription factor. Downstream protein activities that directly regulate longevity during impaired Insulin/IGF-1 signaling (IIS) are poorly characterized. Here, we use global cysteine-reactivity profiling to identify protein-activity changes during impaired IIS. Upon confirming that cysteine reactivity is a good predictor of functionality in C. elegans, we profiled cysteine-reactivity changes between daf-2 and daf-16;daf-2 mutants, and identified 40 proteins that display a >2-fold change. Subsequent RNAi-mediated knockdown studies revealed that lbp-3 and K02D7.1 knockdown caused significant increases in lifespan and dauer formation. The proteins encoded by these two genes, LBP-3 and K02D7.1, are implicated in intracellular fatty-acid transport and purine metabolism, respectively. These studies demonstrate that cysteine-reactivity profiling can be complementary to abundance-based transcriptomic and proteomic studies, serving to identify uncharacterized mediators of C. elegans longevity.

show abstract

Novel Functions of Lipid-binding Protein 5 in Caenorhabditis elegans Fat Metabolism

Cited by 23 publications

References 37 publications

Mutation of the lbp-5 gene alters metabolic output in Caenorhabditis elegans

Mutation of the lbp-5 gene alters metabolic output in Caenorhabditis elegans

Cell-type diversity and regionalized gene expression in the planarian intestine revealed by laser-capture microdissection transcriptome profiling

Global Cysteine-Reactivity Profiling during Impaired Insulin/IGF-1 Signaling in C. elegans Identifies Uncharacterized Mediators of Longevity

Contact Info

Product

Resources

About